Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Sep 2008
Delay of active antimicrobial therapy and mortality among patients with bacteremia: impact of severe neutropenia.
Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. ⋯ In adjusted analysis, among patients in the non-intensive-care-unit setting with an absolute neutrophil count (ANC) of <100 cells/microl, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of <100 cells/microl, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3; P = 0.07). However, for patients who were nonneutropenic (ANC, >500 cells/microl) or had ANCs of 100 to 500 cells/microl, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.
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Antimicrob. Agents Chemother. · Jul 2008
Pharmacokinetics and tissue distribution of anidulafungin in rats.
This study assessed the tissue distribution of anidulafungin in rats. Anidulafungin rapidly distributed into tissues, achieving peak concentrations within 30 min, and maintained levels above MICs for common pathogens over 72 h. In tissues susceptible to fungal infection (liver, lung, spleen, kidney), exposure was 9- to 12-fold higher than in plasma.
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Antimicrob. Agents Chemother. · Jun 2008
Increasing incidence of linezolid-intermediate or -resistant, vancomycin-resistant Enterococcus faecium strains parallels increasing linezolid consumption.
Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r(2) = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.
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Antimicrob. Agents Chemother. · Jun 2008
Comparative StudyDifferential antibiotic susceptibility of Mycobacterium abscessus variants in biofilms and macrophages compared to that of planktonic bacteria.
Mycobacterium abscessus causes refractory pulmonary infections requiring surgery for cure. It exists as a smooth biofilm-forming phenotype which is noninvasive and a rough, non-biofilm-forming phenotype which can invade macrophages and cause persistent pulmonary infection in mice. We have postulated that the dissociation of the smooth phenotype to the rough phenotype may lead to invasive lung disease following initial colonization of the airways. ⋯ In human macrophages, all three antibiotics were only bacteriostatic for M. abscessus variants at 10 times their MICs. These results suggest why treatment failure with antibiotics alone is common in the clinical setting of M. abscessus pulmonary infection. Determination of the efficacies of new antibiotics should include an assessment of their activities against the smooth and rough M. abscessus morphotypes in biofilms and macrophages.